2of3Dr. Harriet Borofsky, a radiologist at Mills-Peninsula Women’s Center in San Mateo, has joined her patients in signing up for a study to test the effectiveness of Grail Inc.’s cancer detection test.Photo: Lea Suzuki / The Chronicle

Dr. Harriet Borofsky, a radiologist and medical director at one of the Bay Area’s largest breast imaging centers, is always on the lookout for technology to improve breast cancer screenings.

She is so hopeful about one such technology — a blood test made by biotech startup Grail Inc. that seeks to detect cancer early — that she recently joined her patients in signing up for a study to test its effectiveness. Mills-Peninsula Women’s Center in San Mateo, where Borofsky works, was one of the first sites to begin enrolling patients in the study and has signed up 3,600 women since 2017. Each submitted a blood sample at the time of their mammogram, and researchers will follow them for five years.

“Right now, we have to screen an entire population of healthy women via mammogram to find early-stage breast cancer,” Borofsky said. “Wouldn’t it be amazing if we had a tool to identify which women need a mammogram? If we had a blood test for early detection of breast cancer, that would really change the landscape of how we screen.”

Grail, a 2-year-old Menlo Park company, has the rare distinction of being a Bay Area biotech unicorn — it has raised $1.5 billion, is valued at nearly $2.5 billion and is one of just six local companies in the health sector with a valuation of $1 billion or more (23andMe is one of them, at $1.5 billion), according to CB Insights.

Grail is also the only company in the same group whose product or service has not yet reached the mass consumer marketplace, which may explain why a firm that has attracted financing from big-name investors like Bill Gates and Jeff Bezos remains largely unknown outside of biotech and investor circles. The study that Borofsky is part of, and a second study in which Grail’s test detected signals in the blood for 20 cancers including lung, ovarian, head and neck and colorectal, are still being conducted and have not produced definitive results.

If Grail is successful, its impact could be felt far beyond Silicon Valley. Doctors could use the test to detect the presence of cancer in the bloodstream before scans and screenings can catch it.

Grail is a ways away from this goal. In the past several months, executives began presenting limited data from clinical studies at medical conferences. The results, they say, are promising, but the patient sample sizes are small and the company has yet to publish peer-reviewed data. Separately, a test to detect nasopharyngeal cancer, which the company planned to introduce in Hong Kong last year, has yet be released; a company spokeswoman said it is looking to work with another entity to market it so Grail can focus on its multi-cancer test. Grail declined to disclose more details about that partnership.

Grail also grappled with a shakeup in executive leadership that led to three CEOs within a span of four months in 2017: Former Google executive Jeff Huber stepped down and then-Chairman Bill Rastetter stepped in until Jennifer Cook took over as the top executive in January 2018. Huber and Rastetter remain on the board of directors, which last month appointed banking veteran Catherine Friedman as chairwoman. Observers say Cook, a well-regarded former Genentech executive, is the right person for the CEO job as the company enters a pivotal year.

“She’s a powerhouse,” said Camille Samuels, a partner at Venrock, which invests in biotech and health startups but has not invested in Grail. “If anyone can solve it, it’s Ms. Cook.”

Grail’s test is designed to detect the presence of what’s known as “circulating DNA” from cancerous tumor cells that have shed into the bloodstream, which looks different than the body’s other DNA. To do so, the company has collected blood samples from tens of thousands of patients, some of whom have a known cancer diagnosis and some of whom do not, to “train” its algorithm to recognize the difference.

Much like Google Images analyzes millions of images to teach itself to distinguish a car from a house, Grail’s algorithm analyzes blood samples to distinguish images of cancer signals in the blood from blood that is cancer-free.

“Google started with a database of images on the internet and used algorithms to learn what distinguishes which features, and categorizes them correctly, and gets better at that over time, with more data,” said Grail co-founder and chief scientific officer Alex Aravanis. “That’s analogous to what we’re doing.”

Doctors such as Borofsky screen an entire population of healthy women via mammogram imaging to find early stage breast cancer. “Wouldn’t it be amazing if we had a tool to identify which women need a mammogram?” Borofksy said.

Photo: Lea Suzuki / The Chronicle

Aravanis came to Grail from Illumina, which provided much of the $100 million in seed funding for and remains a major shareholder of Grail.

Grail’s blood test falls into the category of liquid biopsies, an emerging and promising component of cancer treatment. Rather than extracting a sample from solid tissue like breast or lung, a liquid biopsy takes a blood sample and sequences the DNA of the cancer cells found in the blood to help doctors diagnose the cancer and identify appropriate treatments. It is less invasive than doing a traditional biopsy, which can lead to medical complications, like bleeding or other risks. Other companies, like Redwood City’s Guardant Health, already market this type of test for lung cancer patients.

The technology that Grail is trying to develop, though, would go a step beyond diagnosing and treating cancer to try to detect it early, before any signs or symptoms, in healthy people.

The approach is not without its skeptics. Guardant CEO Helmy Eltoukhy likens it to “trying to get to the top of Mount Everest without getting to base camp.”

Some oncologists are concerned, too. Trying to do early detection in everyone is “a terrible idea,” because it would be too expensive and lead to too many false positives, said Dr. Laura Esserman, a leading breast cancer specialist at UCSF. The more immediate focus, she said, should be on determining which women are at high risk for breast cancer and improving screenings for them.

“This shouldn’t be used for everyone,” Esserman said. “First, we have to figure out who’s at high risk and personalize screening for them.”

Grail acknowledged that false positives are a concern and could lead to alarm and unnecessary procedures. It is aiming for a false positive rate of less than 1 percent.

Health insurance companies don’t have much incentive to pay for an early-detection test because people switch insurers so frequently — as often as every 18 months, said Samuels, the health tech investor.

“A payer only cares about us for a year and a half. They don’t have incentive to find and treat cancer if it’s not going to be a problem in five years, because you won’t be their problem in five years,” she said. “As long as the U.S. doesn’t have single payer, an (insurance company) couldn’t care less if I get breast cancer in five years because I’m not going to be their problem in five years.”

Grail executives hope to sell the test but declined to say when they expect to do so. The company said the Food and Drug Administration, which regulates medical devices including blood tests like Grail’s, allows labs that meet certain state and federal requirements to offer tests without the FDA’s approval. Grail declined to say whether it is seeking FDA approval.

Correction: An earlier version of this story incorrectly stated the status and purpose of a business partnership involving Grail, and what is known about the steps the company is taking in a regulatory process for a test. Grail is seeking to work with another entity in order to market a test in Hong Kong to detect cancer. The company declined to say what regulatory approvals it is seeking in the U.S.

Catherine Ho covers health care and medical technology for the business desk at the San Francisco Chronicle. Before joining the paper in 2017, she worked at The Washington Post, the Los Angeles Times and the legal trade paper the Daily Journal.